Past data from this laboratory supports the following concepts: 1. The urinary bladder of the toad can acidify urine, produce NH4 ion from ammonia precursors, and excrete NH4 ion. 2. The rate of acidification of urine and the rate of excretion of NH4 ion are both increased in response to a metabolic acidosis. 3. Factors prepared from plasma of toads and dogs in metabolic acidosis can increase the rate of H ion and NH4 ion excretion in bladders from toads in normal acid base balance. More recent data have shown the following: 1. Parathyroid hormone (PTH) stimulates H ion excretion in the toad bladder while having no effect on NH4 ion excretion. 2. This effect on H ion excretion by PTH appears to be mediated by cyclic-AMP and in addition, the levels of PTH used seem to be in the physiological range. 3. There is a "factor" extractable from human urine which stimulates NH4 ion excretion in the toad bladder when the subject is in an NH4 Cl induced acidosis (one person). 4. This same factor when injected into the renal artery of a dog will also produce an increased excretion of NH4 ion by the kidney while having no effect on H ion excretion (one dog). Paired hemibladders mounted between lucite chambers were used to obtain the data in items 1-3 above. One hemibladder is a control hemibladder and the other hemibladder from the same toad is the experimental hemibladder. Using these methods we then propose to expand and continue the series of experiments on obtaining this factor from the urine of other human subjects and to improve the extraction procedure for obtaining the factor. We propose to determine if circulating PTH levels are increased in the toad in response to a metabolic acidosis and at the same time determine if the cyclic-AMP are increased in the mucosal cells of the toad urinary bladder during acidosis. We also propose to do a correlative study on the scanning electron micrograph findings compared with changes in transmission electron micrographs of the toad bladder mucosal cells, while in metabolic acidosis. Finally, we propose to determine if the factor is active in the mammalian nephron as well as the toad bladder by infusing it into the renal artery of the dog.